Biology subjects

Russ, B. E.

Publications and source records attributed to Russ, B. E..

At least 19 recordsLinked to original sources

bioRxiv2026

During natural vision, semantic novelty modulates fixation-related processing in primate cortex

We sample visual scenes with short gaze fixations separated by saccades. While low-level integration is known, semantic integration of foveal vision across fixations remains unclear. We hypothesized that the brain responds to changes in semantic information from one fixation to the next, and therefore postulated a neural signal associated with semantic novelty for each saccade. Novelty was measured from different layers of a deep network on foveal vision. Only semantic, and not low- or mid-level, novelty modulated frontal and occipital fixation-related potentials in male and female human scalp EEG during natural viewing of full-length movies (3.4x106 saccades). Intracranial recordings in male and female humans (9.0x104 saccades) and female non-human primates (Macaca mulatta; 3.3x104 saccades) revealed broadband high-frequency activity modulations in scene-specific ventral visual and frontal brain areas only for semantic novelty. This modulation was stronger for movies than static images, and frontal modulation occurred early alongside occipital modulation, suggesting top-down effects. This modulation of fixation-related activity with novelty suggests that foveal representations are integrated across fixations to construct scene representations during natural viewing in primates.

neuroscience↗

bioRxiv2026

Dose-dependent power and connectivity modulation of low frequency oscillations through transcranial magnetic stimulation in non-human primates.

Transcranial magnetic stimulation (TMS) is a powerful non-invasive tool for safely modulating neural activity in humans. In particular, the left dorsolateral prefrontal cortex (DLPFC) is a common target site for clinical interventions in disorders such as treatment-resistant depression. Yet, clinical trials investigating the efficacy of TMS often lack neural markers of target engagement of the DLPFC. Local field potentials (LFPs), such as prefrontal theta oscillations, have been implicated in the clinical symptoms of these disorders. However, non-invasive electroencephalography (EEG) recordings in humans are limited by their spatial resolution and challenges of interpreting EEG signals. In this study, we investigate the effects of single-pulse TMS applied to the left prefrontal cortex in non-human primates on LFPs recorded through intracranial EEG. Compared to sham TMS, the intensity of active TMS pulses scaled with LFP power changes in a 1-13 Hz range at contacts close to the stimulation site in the prefrontal cortex (e.g., caudate nucleus, anterior cingulate cortex, insular cortex) as well as contacts that were more distal (e.g., posterior cingulate cortex, temporal lobe). To test how TMS modulates connectivity between these regions, we conducted a phase-based connectivity analysis. TMS pulses initially enhanced and then disrupted connectivity at 1-13 Hz between the stimulation site and other contacts. Connectivity rebounded approximately 1500 ms post-stimulation. Only the initial enhancement in connectivity scaled with TMS intensity. Our results demonstrate a dose-dependent power modulation of low frequency LFPs across prefrontal, parietal and temporal cortical regions by single pulses. Furthermore, they show that TMS applied over the left prefrontal cortex can enhance and interrupt short- and long-range connectivity. Our study advances the understanding of the effects of TMS on brain oscillations and connectivity with direct relevance for clinical applications in neuromodulation therapies.

neuroscience↗

bioRxiv2025

SATB1 maintains naive-like identity in antiviral CD8⁺ T cells by limiting chromatin remodelling at effector gene loci.

Optimal CD8+ T cell differentiation requires the engagement of transcriptional programs that drive effector phenotypes and function, whilst also shutting down transcriptional programs that maintain the naive state. While the distinct factors that underpin each state are well studied, the molecular mechanisms that control the switch from the naive to effector state are not fully understood. Utilising integrated analysis of single-cell genomic data, we identified CD8+ T cell effector transcriptional networks that are restrained in the naive state by the chromatin binding protein Special AT-rich sequence binding protein-1 (SATB1). Utilising a SATB1-Tg model, whereby activated CD8+ T cells are unable to down regulate SATB1 upon activation, we observed limited effector differentiation and an inability to engage effector programs in response to both primary and secondary influenza A virus infection. Mechanistically, SATB1 limited chromatin remodelling at key gene loci required for the full engagement of the CD8+ T cell effector program. Hence, SATB1 is a master gatekeeper that maintains the naive T cell state and whose downregulation is necessary to allow transition from a naive to effector state upon T cell activation. SATB1 modulation may provide new strategies for improving CD8+ T cell longevity and self-renewal capacity in different immunotherapeutic treatments.

immunology↗

bioRxiv2024

Ventrolateral prefrontal cortex in macaques guides decisions in different learning contexts

Flexibly adjusting our behavioral strategies based on the environmental context is critical to maximize rewards. Ventrolateral prefrontal cortex (vlPFC) has been implicated in both learning and decision-making for probabilistic rewards, although how context influences these processes remains unclear. We collected functional neuroimaging data while rhesus macaques performed a probabilistic learning task in two contexts: one with novel and another with familiar visual stimuli. We found that activity in vlPFC encoded rewards irrespective of the context but encoded behavioral strategies that depend on reward outcome (win-stay/lose-shift) preferentially in novel contexts. Functional connectivity between vlPFC and anterior cingulate cortex varied with behavioral strategy in novel learning blocks. By contrast, connectivity between vlPFC and mediodorsal thalamus was highest when subjects repeated a prior choice. Furthermore, pharmacological D2-receptor blockade altered behavioral strategies during learning and resting-state vlPFC activity. Taken together, our results suggest that multiple vlPFC-linked circuits contribute to adaptive decision-making in different contexts.

neuroscience↗

bioRxiv2024

Brain Charts for the Rhesus Macaque Lifespan

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

neuroscience↗

bioRxiv2024

Deep brain stimulation induces white matter remodeling and functional changes to brain-wide networks

Deep brain stimulation (DBS) is an emerging therapeutic option for treatment resistant neurological and psychiatric disorders, most notably depression. Despite this, little is known about the anatomical and functional mechanisms that underlie this therapy. Here we targeted stimulation to the white matter adjacent to the subcallosal anterior cingulate cortex (SCC-DBS) in macaques, modeling the location in the brain proven effective for depression. We demonstrate that SCC-DBS has a selective effect on white matter macro- and micro-structure in the cingulum bundle distant to where stimulation was delivered. SCC-DBS also decreased functional connectivity between subcallosal and posterior cingulate cortex, two areas linked by the cingulum bundle and implicated in depression. Our data reveal that white matter remodeling as well as functional effects contribute to DBSs therapeutic efficacy.

neuroscience↗

bioRxiv2023

Pharmacological modulation of dopamine D1 and D2 receptors reveals distinct neural networks related to probabilistic learning in non-human primates.

The neurotransmitter dopamine (DA) has a multifaceted role in healthy and disordered brains through its action on multiple subtypes of dopaminergic receptors. How modulation of these receptors influences learning and motivation by altering intrinsic brain-wide networks remains unclear. Here we performed parallel behavioral and resting-state functional MRI experiments after administration of two different DA receptor antagonists in macaque monkeys. Systemic administration of SCH-23390 (D1 antagonist) slowed probabilistic learning when subjects had to learn new stimulus-reward associations and diminished functional connectivity (FC) in cortico-cortical and fronto-striatal connections. By contrast, haloperidol (D2 antagonist) improved learning and broadly enhanced FC in cortical connections. Further comparisons between the effect of SCH-23390/haloperidol on behavioral and resting-state FC revealed specific cortical and subcortical networks associated with the cognitive and motivational effects of DA manipulation, respectively. Thus, we reveal distinct brain-wide networks that are associated with the dopaminergic control of learning and motivation via DA receptors. Significance StatementD1 and D2 receptors are heavily implicated in cognitive and motivational processes, as well as in a number of psychiatric disorders. Despite this, little is known about how selective manipulation of these different receptors impacts cognition through changing activity across brain-wide intrinsic networks. Here, we examined the acute behavioral and brain-wide effects of D1 and D2 receptor-selective antagonists, SCH-23390 and haloperidol, in macaques performing a probabilistic learning task. SCH administration diminished, and haloperidol improved, animals task performance. Mirroring these effects on behavior, SCH reduced, and haloperidol increased, the resting-state functional connectivity across brain-wide networks, most notably in the cortico-striatal areas. Thus, our results highlight the opposing effects of D1 and D2 receptor modulation on the brain and behavior.

neuroscience↗

bioRxiv2023

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the macaque amygdala and activated them with a highly selective and potent DREADD agonist, deschloroclozapine. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Interestingly, activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-disciplinary approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

neuroscience↗

bioRxiv2023

Active maintenance of CD8+ T cell naivety through regulation of global genome architecture

The differentiation of naive CD8+ cytotoxic T lymphocytes (CTLs) into effector and memory states results in large scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organisation reflect or underpin these transcriptional programs. We utilised Hi-C to map changes in the spatial organisation of long-range genome contacts within naive, effector and memory virus-specific CD8+ T cells. We observed that the architecture of the naive CD8+ T cell genome was distinct from effector and memory genome configurations with extensive changes within discrete functional chromatin domains. However, deletion of the BACH2 or SATB1 transcription factors was sufficient to remodel the naive chromatin architecture and engage transcriptional programs characteristic of differentiated cells. This suggests that the chromatin architecture within naive CD8+ T cells is preconfigured to undergo autonomous remodelling upon activation, with key transcription factors restraining differentiation by actively enforcing the unique naive chromatin state. One Sentence SummaryCD8+ T cell naivety is actively maintained by transcription factors that enforce a distinct, naive chromatin architecture. HighlightsO_LICD8+ T cell differentiation states are underscored by distinct chromatin looping architectures. C_LIO_LIChromatin loops juxtapose CTL state appropriate enhancers, transcription factors and genes. C_LIO_LIEffector and memory CTLs have similar genome architectures, explaining rapid memory recall. C_LIO_LICTL differentiation is restrained by BACH2 and SATB1, which enforce a naive loop architecture. C_LI

immunology↗

bioRxiv2023

High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex

The basolateral amygdala (BLA) projects widely across the macaque frontal cortex1-4, and amygdalo-frontal projections are critical for optimal emotional responding5 and decision- making6. Yet, little is known about the single-neuron architecture of these projections: namely, whether single BLA neurons project to multiple parts of the frontal cortex. Here, we use MAPseq7 to determine the projection patterns of over 3000 macaque BLA neurons. We found that one-third of BLA neurons have two or more distinct targets in parts of frontal cortex and of subcortical structures. Further, we reveal non-random structure within these branching patterns such that neurons with four targets are more frequently observed than those with two or three, indicative of widespread networks. Consequently, these multi-target single neurons form distinct networks within medial and ventral frontal cortex consistent with their known functions in regulating mood and decision-making. Additionally, we show that branching patterns of single neurons shape functional networks in the brain as assessed by fMRI-based functional connectivity. These results provide a neuroanatomical basis for the role of the BLA in coordinating brain-wide responses to valent stimuli8 and highlight the importance of high- resolution neuroanatomical data for understanding functional networks in the brain.

neuroscience↗

bioRxiv2022

Mesoscale neural effects of transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent direct neural mechanisms, i.e., due to electric field or connectivity, and peripheral sensory co-stimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging due to the limited spatiotemporal resolution of available non-invasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in non-human primates to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response with stimulation intensity. We further show that stimulation responses are spatially specific. We employ several control conditions to dissociate direct neural responses from auditory and somatosensory co-activation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications.

neuroscience↗

bioRxiv2022

Naturalistic viewing: An open-access dataset using simultaneous EEG-fMRI

In this work, we present a dataset that combines functional magnetic imaging (fMRI) and electroencephalography (EEG) to use as a resource for understanding human brain function in these two imaging modalities. The dataset can also be used for optimizing preprocessing methods for simultaneously collected imaging data. The dataset includes simultaneously collected recordings from 22 individuals (ages: 23-51) across various visual and naturalistic stimuli. In addition, physiological, eye tracking, electrocardiography, and cognitive and behavioral data were collected along with this neuroimaging data. Visual tasks include a flickering checkerboard collected outside and inside the MRI scanner (EEG-only) and simultaneous EEG-fMRI recordings. Simultaneous recordings include rest, the visual paradigm Inscapes, and several short video movies representing naturalistic stimuli. Raw and preprocessed data are openly available to download. We present this dataset as part of an effort to provide open-access data to increase the opportunity for discoveries and understanding of the human brain and evaluate the correlation between electrical brain activity and blood oxygen level-dependent (BOLD) signals.

neuroscience↗

bioRxiv2022

Semantic novelty modulates neural responses to visual change across the human brain

Our continuous visual experience in daily life is dominated by change. Previous research has focused on visual change due to stimulus motion, eye movements or unfolding events, but not their combined impact across the brain, or their interactions with semantic novelty. We investigate the neural responses to these sources of novelty during film viewing. We analyzed intracranial recordings in humans across 6328 electrodes from 23 individuals. Responses associated with saccades and film cuts were dominant across the entire brain. Film cuts at semantic event boundaries were particularly effective in the temporal and medial temporal lobe. Saccades to visual targets with high visual novelty were also associated with strong neural responses. Specific locations in higher-order association areas showed selectivity to either high or low-novelty saccades. We conclude that neural activity associated with film cuts and eye movements is widespread across the brain and is modulated by semantic novelty.

neuroscience↗

bioRxiv2022

Saccadic modulation of neural excitability in auditory areas of the neocortex

SummaryIn natural "active" vision, humans and other primates use eye movements (saccades) to sample bits of information from visual scenes. In this process, nonretinal signals linked to saccades shift visual cortical neurons to a high excitability state as each saccade ends. The extent of this saccadic modulation outside of the visual system is unknown. Here, we show that during natural viewing, saccades modulate excitability in numerous auditory cortical areas, with a pattern complementary to that seen in visual areas. Bi-directional functional connectivity patterns suggest that these effects may arise from regions involved in saccade generation. By using saccadic signals to yoke excitability states in auditory areas to those in visual areas, the brain can improve information processing in complex natural settings.

neuroscience↗

bioRxiv2022

Temporal continuity shapes visual responses of macaque face patch neurons

Macaque inferior temporal cortex neurons respond selectively to complex visual images, with recent work showing that they are also entrained reliably by the evolving content of natural movies. To what extent does visual continuity itself shape the responses of high-level visual neurons? We addressed this question by measuring how cells in face-selective regions of the macaque temporal cortex were affected by the manipulation of a movies temporal structure. Sampling the movie at 1s intervals, we measured neural responses to randomized, brief stimuli of different lengths, ranging from 800 ms dynamic movie snippets to 100 ms static frames. We found that the disruption of temporal continuity strongly altered neural response profiles, particularly in the early onset response period of the randomized stimulus. The results suggest that models of visual system function based on discrete and randomized visual presentations may not translate well to the brains natural modes of operation.

neuroscience↗

bioRxiv2021

Resting-state fMRI-based screening of deschloroclozapine in rhesus macaques predicts dosage-dependent behavioral effects

Chemogenetic techniques such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) enable transient, reversible, and minimally invasive manipulation of neural activity in vivo. Their development in non-human primates is essential for uncovering neural circuits contributing to cognitive functions and their translation to humans. One key issue that has delayed the development of chemogenetic techniques in primates is the lack of an accessible drug-screening method. Here, we utilize resting-state functional MRI (rs-fMRI), a non-invasive neuroimaging tool, to assess the impact of deschloroclozapine (DCZ) on brain-wide resting-state functional connectivity in seven rhesus macaques without DREADDs. We found that systemic administration of 0.1 mg/kg DCZ did not alter the resting-state functional connectivity. Conversely, 0.3 mg/kg of DCZ was associated with a prominent increase in functional connectivity that was mainly confined to the connections of frontal regions. Additional behavioral tests confirmed a negligible impact of 0.1 mg/kg DCZ on socio-emotional behaviors as well as on reaction time in a probabilistic learning task. 0.3 mg/kg DCZ did, however, slow responses in the probabilistic learning task, suggesting attentional or motivational deficits associated with hyperconnectivity in fronto-temporo-parietal networks. Our study highlights both the excellent selectivity of DCZ as a DREADD actuator, and the side-effects of its excess dosage. The results demonstrate the translational value of rs-fMRI as a drug-screening tool to accelerate the development of chemogenetics in primates.

neuroscience↗

bioRxiv2021

Parallel functional subnetworks embedded in the macaque face patch system

During normal vision, our eyes provide the brain with a continuous stream of useful information about the world. How visually specialized areas of the cortex, such as face-selective patches, operate under natural modes of behavior is poorly understood. Here we report that, during the free viewing of videos, cohorts of face-selective neurons in the macaque cortex fractionate into distributed and parallel subnetworks that carry distinct information. We classified neurons into functional groups based on their video-driven coupling with fMRI time courses across the brain. Neurons from each group were distributed across multiple face patches but intermixed locally with other groups at each recording site. These findings challenge prevailing views about functional segregation in the cortex and underscore the importance of naturalistic paradigms for cognitive neuroscience. One-Sentence SummaryNatural visual experience reveals parallel functional subnetworks of neurons embedded within the macaque face patch system

neuroscience↗

bioRxiv2020

KDM6B-dependent chromatin remodelling underpins effective virus-specific CD8+ T cell differentiation.

Naive CD8+ T cell activation results in an autonomous program of cellular proliferation and differentiation. However, the mechanisms that underpin this process are unclear. Here we profiled genome-wide changes in chromatin accessibility, gene transcription and the deposition of a key chromatin modification (H3K27me3) early after naive CD8+ T cell activation. Rapid upregulation of the histone demethylase, KDM6B, prior to first cell division was required for initiating H3K27me3 removal at genes essential for subsequent T cell differentiation and proliferation. Inhibition of KDM6B-dependent H3K27me3 demethylation limited the magnitude of an effective primary virus-specific CD8+ T cell response and the formation of memory CD8+ T cell populations. Accordingly, we define the early spatio-temporal events underpinning early lineage-specific epigenetic reprogramming that is necessary for autonomous CD8+ T cell proliferation and differentiation.

immunology↗